Triple combination therapies for Anti-aging

An anti-aging and therapeutic agent technology, applied in anti-tumor drugs, cosmetic preparations, medical preparations with inactive ingredients, etc.

Inactive Publication Date: 2021-09-28
LUNELLA BIOTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Anti-mitochondrial side effects are generally considered undesired by modern m

Method used

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  • Triple combination therapies for Anti-aging
  • Triple combination therapies for Anti-aging
  • Triple combination therapies for Anti-aging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0105] The following compounds [12B], [13B] and [14B] show specific examples of conjugates of erythromycin family members according to this approach and use the general structure of the second series shown above. In compound [12B], R 1 fatty acid moiety The general structural substitution of , wherein "n" is an integer from 1 to 20, preferably 10 to 20, and other substitution positions have the normal components present on the structure of azithromycin. In compound [13B], R 2 has been substituted by the same general structure of the fatty acid moiety as in compound [12B], while another substituted position R 1 Has the normal constituents present on the structure of roxithromycin. As an example based on the second telithromycin conjugate formula, compound [14B] in R 1 have the same general structure of fatty acids, while NH-R 2 Conversely, the N(CH 3 ) 2 . In these examples, "n" is an integer of 1-20, preferably 10-20. For example, embodiments of erythromycin and fatt...

Embodiment 1

[0121] Example 1 - Conjugates of doxycycline and fatty acids. (4S,5S,6R,12aS)-4-(Dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-9-(tetradecyl Acylamino)-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide (i.e., as described above in R 9 doxycycline conjugated to myristic acid and is shown below as compound [18]). 9-aminodoxycycline (prepared as described in Barden, Timothy C. et al. "Glycylcyclines". 3.9-Aminodoxycyclinecarboxamides. J. Med. Chem. 1994, 37, 3205-3211) (0.70 g, 1.5 mmol) , tetradecanoic acid (0.36g, 1.5mmol), HBTU (0.85g, 2.25mmol) and NMM (0.33ml, 3.0mmol) in the mixture of DCM (12ml) and DMF (4ml) solution in nitrogen atmosphere Stir at room temperature for 72 hours. The solvent was evaporated under reduced pressure. The resulting residue was triturated with acetonitrile (40ml) and the precipitate was collected by filtration, washed with acetonitrile (10ml), diethyl ether (20ml) and dried under vacuum. The crude product was dissolved in DMSO ...

Embodiment 2

[0123] Example 2 - Conjugates of doxycycline and fatty acids. (4S,5S,6R,12aS)-4-(Dimethylamino)-9-(hexadecanoylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11- Dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide. Compound [19] shown below was prepared according to the method in Example 1. LC-MS 698.2[M+H] + ,RT3.02min.

[0124]

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PUM

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Abstract

The present approach effectively eradicates senescent cells and cells carrying the hallmarks associated with aging, through inhibiting mitochondrial biogenesis during induced mitochondrial oxidative stress, without inhibiting normal cells. Embodiments may include a therapeutic agent that inhibits mitochondrial biogenesis and targets the large mitochondrial ribosome, a therapeutic agent that inhibits mitochondrial biogenesis and targets the small mitochondrial ribosome, and a therapeutic agent that behaves as a pro-oxidant or induces mitochondrial oxidative stress. Some embodiments include sub-antimicrobial antibiotic concentrations, thereby minimizing antibiotic resistance concerns.

Description

technical field [0001] The present disclosure relates to compositions and methods for anti-aging and other beneficial therapeutic uses. Background technique [0002] The biological process of aging continues to receive considerable attention from the scientific and medical research community. Physiological aging is associated at least in part with increased rates of oxidative damage to cellular components, including DNA, lipids, proteins, and the like. Increased oxidative damage creates an imbalance that disrupts autoregulatory processes at the cellular level. Furthermore, aging is associated with the accumulation of lipofuscin in the cytoplasm of neurons. Modern research also suggests that aging is the result of naturally occurring DNA damage leading to abnormal DNA changes that accumulate over time. Both mitochondrial and nuclear DNA damage can promote aging indirectly by increasing apoptosis and cellular senescence, and directly by increasing cellular dysfunction. Acc...

Claims

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Application Information

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IPC IPC(8): A61K31/65A61P35/00A61K31/00
CPCA61K31/65A61P35/00A61K45/06A61K31/7052A61K31/375A61K31/7048A61K8/676A61K8/42A61K8/361A61K2800/57A61Q7/00A61K8/498A61K2300/00A61K47/542A61K47/548A61K41/0038A61K31/166A61K31/05C07F9/5442
Inventor M·P·利桑蒂F·苏特加M·菲奥里罗
Owner LUNELLA BIOTECH INC
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